Low-sulphated oligosaccharides derived from heparan sulphate inhibit normal angiogenesis

Area of Science:

• Biochemistry
• Molecular Biology
• Developmental Biology

Background:

• Heparin and related glycosaminoglycans play roles in biological processes.
• Angiogenesis, the formation of new blood vessels, is crucial for development and disease.
• The specific structural components of heparin responsible for its biological effects are not fully understood.

Purpose of the Study:

• To identify the specific saccharide structure responsible for the anti-angiogenic activity of heparin.
• To investigate the anti-angiogenic potential of non-sulphated heparin fragments and related polysaccharides.
• To explore the role of heparan sulphate proteoglycans in angiogenesis regulation.

Main Methods:

• Inhibition of angiogenesis in chick embryo chorioallantoic membrane assay.
• Testing of various heparin fragments, Escherichia coli K5 polysaccharide, and hyaluronan.
• Analysis of structure-activity relationships, including sulphation and specific sugar sequences.

Main Results:

• Heparin and low- or non-sulphated fragments demonstrated anti-angiogenic effects.
• The -[GlcA beta 1,4-GlcNAc alpha 1,4]n- sequence was identified as crucial for anti-angiogenic activity.
• Escherichia coli K5 polysaccharide and its fragments showed significant anti-angiogenic activity, unlike hyaluronan.

Conclusions:

• The -[GlcA beta 1,4-GlcNAc alpha 1,4]n- structure is a key determinant of anti-angiogenic activity in heparin and related saccharides.
• Non-sulphated heparin fragments and bacterial polysaccharides with this structure can inhibit angiogenesis.
• Heparan sulphate proteoglycans may serve as precursors for anti-angiogenic oligosaccharides regulating blood vessel formation.